Myasthenia Gravis (MG) is one of the best-understood autoimmune diseases affecting human beings. In literal terms, the term myasthenia means muscle weakness, and gravis means seriously or extremely. So the term myasthenia gravis implies a condition causing serious muscle weakness.

How common is MG?

It is not a common disease, and probably affects 1 out of 5,000 people.

 

What are the symptoms of MG?

Most common symptom of MG is droopiness of eyelid, either one or both. Symptoms appear first in eye muscles more than others, probably due to the sensitive task these muscles perform. Eye movements require exquisite muscle alignment with precision to move both eyes together, like they are yoked. If any of the eye muscle is weak, that eye may lag behind and the patient may start seeing two separate images, one from each eye. The patient may come with symptom of droopiness of eyelid, and/or seeing double. Following are common symptoms of MG:

            . Droopiness of eyelid(s)

            . Double vision

            . Difficulty swallowing

            . Difficulty breathing

            . Generalized muscle weakness

            . Difficulty walking

            . Fatigue

Of note, MG does not cause any pain or headache, numbness or tingling, or any mental or cognitive symptoms.

 

What other conditions may present with symptoms similar to MG?

Some conditions that may mimic MG are:

            . Stroke

            . Brain aneurysm

            . Local neuropathy or a cranial nerve problem

            . Muscle disorders like muscular dystrophy

            . Peripheral neuropathy

            . Parkinson disease like conditions

            . ALS

 

How do symptoms of MG differ from other conditions?

There are many clear differences. For example, droopiness of eyelid from a stroke or nerve injury does not fluctuate, as it does in MG. Patient may have less droopiness in morning hours than evening hours, or more when tired. Also, double vision of MG may fluctuate too based upon time of the day.

MG does not affect pupil size, while a problem with a nerve or an aneurysm may affect the pupil size.

In spite of these differences, it is not uncommon, especially in early stages of MG, to have a misdiagnosis. Further testing is done for clarification.

 

What exactly is the problem in MG?

MG is a problem with muscles that can be voluntarily controlled. While it is a problem with muscles, it is not a problem of muscle cells. This means that muscles are affected but not because of a muscle disease. They are indirectly affected. Muscles are normally controlled through signals coming from brain. These electric signals are transmitted through nerves to each and every muscle. When these electrical signals reach a muscle, they do not directly reach a muscle cell as an electric charge. Instead, they pass through a complex process that converts the electrical signal to a biochemical one. This conversion takes place at tiny structures on the muscle fibers called neuromuscular junctions, which in a way are acting as transducers. Myasthenia Gravis (MG) is a defect of these microscopic transducers or neuromuscular junctions.

For anyone looking for more detail, here are few more words. The neuromuscular junction or the transducer has two ends, one on the nerve side and the other on the muscle, like a plug and a switch. MG is the problem on the muscle side of this structure. There are tiny structures on that end called acetylcholine receptors. In a patient with MG, antibodies attach themselves to these structures (so is the reason these antibodies are called acetylcholine receptor antibodies), and they cannot function. After sometime, these structures with their attached antibodies are attacked by the body’s own immune system and are destroyed. This leads to lowering in number of these receptors and weakening of these structures.

With significant receptors destroyed, a patient may start noticing weakness. Weakness appears first in muscles that are more sensitive, or controlling sensitive structures, like eye muscles. Many antibodies have been identified, but there can still be some patients with MG with a type of antibody not yet known. To make a distinction, patients who have the identifiable antibody are called antibody-positive, and the ones without are called antibody-negative myasthenia gravis patients. At this time, almost 1/4^th patients with MG do not have an identifiable antibody.

 

How is MG diagnosed?

In many patients, its presentation is so typical that one almost is certain about the diagnosis right away. Even then, some tests are required to make a definite diagnosis. Following tests can help:

A: Ice-pack test: Exposing eyelids to cold with an ice-pack for 2-5 minutes may reverse ptosis. This test has sensitivity and specificity of about 85%.

B: Tensilon test: Tensilon is the original brand name of a drug called edrophonium chloride. An intravenous injection of this drug can promptly correct the muscle weakness of MG. But our body neutralizes this drug in a minute or two and the effect goes away. This test can only be used if one can reliably assess a muscle function, and may not be useful in doubtful cases. For example, a fully drooped eyelid is easy to monitor and assess. Classically, to avoid any confusion or bias, the test is done in a double-blinded fashion with patient or the doctor not knowing which syringe has the medicine. The test is positive if the drug resolves the weakness, even if transiently. A positive Tensilon test can make the diagnosis of myasthenia gravis. In recent years, it is getting difficult to obtain this drug resulting in less frequent use of the test.

C: Antibody test: Antibodies causing MG can be detected by a simple blood test. One of the antibody tests is usually positive in majority of cases of MG. Typically, acetylcholine antibody receptor blocking, binding, and modulating antibody levels are ordered. If they are negative, one may also try anti-Musk and anti-LRP4 antibody titers.

D: Electrophysiological testing: Presence of certain electrical findings may support this diagnosis. With a typical clinical picture, these findings can help to make the diagnosis, especially in a patient whose antibody testing is negative. Both nerve conduction studies, NCS, and electromyogram, EMG, can help. NCS may reveal a decremental response to repetitive stimulation, while single fiber EMG findings can suggest MG, but are not specific to MG. Another issue is that part of the electrical testing, the single fiber EMG, is more specialized, and may not be available at every neurology office.

E: Chest CT scan: It is customary to perform chest CT to rule thymoma (a benign tumor or thymus), or just its enlargement. Thymoma is a small gland behind our sternum. If it is enlarged, it is taken out, which in many patients can either resolve MG or make it significantly better.

 

Is there a natural remedy for MG?

No natural remedy has proven to show any benefit in MG. Similarly, no particular dietary change or treatment is proven to make any difference.

 

Why treatment is required for MG?

MG is an autoimmune disease. Once symptoms appear, it can gradually worsen. Little bit of droopiness of eyelid may not be an issue, but the double vision can cause a problem. Also, in many patients it may spread to other muscles that control swallowing or breathing, resulting in life-threatening situations. While untreated MG can be life threatening, it is a very treatable condition.

 

How is MG treated?

Many medicines and techniques are available to treat MG. Following are the more common ones:

1. Symptomatic treatment: This type of medicine does not change the course of the disease. It provides temporary relief from symptoms.

Pyridostigmine (Mestinon): It works quickly, in about 30 minutes, and the effect does not last long, only for 3-4 hours. The patient has to take multiple doses for continued relief. Most people tolerate it without any significant issues. Common side effects are loose stools, salivation, nausea, and abdominal cramps. It can also cause low blood pressure and slow heart rate. Typical dose is 60mg 2-6 times daily.

2. Immune modulating agents: These drugs can change the course of disease, and help control it. They work by tweaking the immune system so that it stops attacking body’s own structures.

a. Prednisone: It takes weeks to kick in, and when it works, and in majority of cases it does, the effect is long lasting. It is a steroid, which may have number of side effects and sometimes complications. More common issues with prednisone, if they occur, are high glucose level, weight gain, insomnia, anxiety, irritability, infections, thinning of bones causing osteoporosis, bone fracture, confusion, etc. In spite of its multiple risks, prednisone is a very useful medicine for MG. It is used when its benefit outweighs its risk. This may not be the case in a patient with out of control diabetes, in which case alternate medicines are available. Prednisone is typically started at higher dose of 40-80 mg daily. After a few weeks, the dose is slowly decreased to a minimum effective dose. Many of my patients are taking 0.5 to 2 mg a day as maintenance treatment. At this dose, side effects of prednisone are minimal.

b. Azathioprine: It is a chemotherapy agent. It takes weeks to months to kick in. This type of medicines is considered when a patient either does not respond to prednisone or does not tolerate it. In some ways, it is a much easier medicine to take compared to prednisone with limited immediate side effects, and no impact on weight or blood sugar. The risk with this medicine is due to its effect on the bone marrow, which may impact blood cell count. This is the reason that a blood test is routinely done to monitor any serious reduction in blood cell count. Potentially, there are numerous other serious side effects, such as liver toxicity or pancreatitis. Many times, it is given in combination with prednisone. In terms of effectiveness, it is not as effective as prednisone.

c. Mycophenolate mofetil: It is also a chemotherapy agent. It takes weeks to months to kick in. Like azathioprine, it can also have significant side effects, especially its impact on blood cell count. But side effects are somewhat less than azathioprine. Regular blood tests are required to monitor any toxicity.

d. Cyclosporine: Serial CBC requires. It is a teratogenic drug.

e. Tacrolimus: It may cause hyperglycemia, hypomagnesemia, and kidney damage.

f. Methotrexate: Can be toxic to liver. Regular blood tests required.

g. Cyclophosphamide: Teratogenic drug, regular blood tests required.

3. Intravenous immunoglobulin (IVIg): This is the plasma part of blood, collected from the donated blood after red blood cells are separated. It is given as intravenous infusion. Common risks are allergies, kidney overload (due to high amount of protein), and headaches. It is used in combination with oral treatment. In terms of efficacy, it is quite effective, especially in emergency situation. It kicks in within days.

4. Plasmapheresis: This is a procedure similar to dialysis. Patient is attacked to a machine that draws patient’s blood, removes some of the antibodies from it, and delivers it back to the patient. The procedure is done in a hospital and a session may take hours. It is done to remove some antibodies that may be causing the disease. For most cases of MG, it is not a routine treatment and is only used if other measures fail. But in some particular cases, such as patients with positive anti-Musk antibody, it can be more helpful.

5. Biological drugs: There are many in this category such as ritixuimab, eculizumab, ravulizumab, and efgartigimod. They are promising drugs for many patients resistant to initial treatment, and may before trying chemotherapeutic drugs.

6. Surgery: Removing thymus gland can also help. Thymus is a small gland behind our sternum. Its enlargement can be diagnosed with a chest CT, and it can be removed either by open chest surgery, or through a smaller hole in the chest.

 

Can MG affect children?

Rarely it can. It can also affect newborns. The subject of diagnosis of MG in newborns and young children is somewhat more complicated and not discussed here.

 

Is MG a terminal illness?

It can be if not treated. With treatment, it can be managed.

 

Is treatment of MG temporary or life-long?

In most cases, it is life-long. Sometimes, especially in mild cases, removing thymus gland can alleviate the disease.

 

Where can I get more information about MG?

American Academy of Neurology

Center for Disease Control and Prevention